Gastric and duodenal ulcers are gastro intestinal diseases caused by various factors such as mental stress, dietary habits, intake of irritable food etc. The ulcers are caused due to damage of gastric membrane because of excess secretion of gastric acid.
The therapeutic agents which have been commonly used for the treatment of ulcers are antacids for neutralizing gastric acid, antipepsin agents for protecting the gastric mucous membrane and anticholinergic agents for inhibiting gastric acid secretion. At the present time, Histamine-H.sub.2 -receptor antagonists have been widely used for treating gastric and duodenal ulcers.
More recently, proton pump inhibitors are gaining importance since they block the proton pump of H.sup.+ /K.sup.+ -ATPase, an enzyme specifically present in the parietal cells of the stomach to inhibit the gastric acid secretion at the final stage. One of the earliest proton pump inhibitors is 2-[[(4-methoxy-3,5-dimethyl)pyridin-2-yl]methylsulfinyl]-5-methoxy-1H-b enzimidazole whose generic name is Omeprazole (see Patent Application. Nos. EP 0 005 129; JP 79,141,783 and U.S. Pat. No. 4,255,43 1) having the following, formula (II) which is being, used to treat the above mentioned disease conditions. ##STR3##
A wide variety of compounds related to Omeprazole having a pyridylmethylsulfinyl benzimidazole structure are described in various patent documents.
A group of compounds having general formula (IIa) wherein R.sup.1 represents hydrogen, methoxy or trifluoromethyl, R.sup.2 and R.sup.3 independently represent hydrogen or methyl, R.sup.4 represents fluoroalkyl and n is an integer of 0 to 1 have been described in European Patent application No. 0 174 726. ##STR4## An example of these compounds is Lansoprazole shown in formula (IIb). ##STR5##
A group of compounds having general formula (IIc) wherein R.sup.1 represents (C.sub.1 -C.sub.3)alkyl which is completely or predominantly substituted by fluorine or a chlorodifluoromethyl radical, R.sup.2 represents hydrogen, halo, trifluoromethyl, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy which is completely or predominantly substituted by fluorine, R.sup.1 and R.sup.2 together with the oxygen atom to which R.sup.1 is bonded are (C.sub.1 -C.sub.2)alkylenedioxy which is optionally or completely substituted by fluorine or chlorotrifluoroethylenedioxy, one of R.sup.3 and R.sup.5 represents (C.sub.1 -C.sub.3)alkoxy and the other represents hydrogen atom or (C.sub.1 -C.sub.3)alkyl, and the R.sup.4 is (C.sub.1 -C.sub.3)alkoxy and n is an integer of 0 to 1 are disclosed in U.S. Pat. No. 4,758,579. ##STR6## An example of these compounds is Pantoprazole shown in formula (IId) ##STR7##
A group of compounds having general formula (IIe) where J, K represents hydrogen or alkyl, R.sup.1, R.sup.2 represents hydrogen, alkyl, alkoxy, halo, haloalkyl, alkoxycarbonyl or CO.sub.2 H, X represents oxygen, sulfur or NR.sup.3, where R.sup.3 represents hydrogen, alkyl, Ph, PhCH.sub.2 or alkoxycarbonyl, Z represents O(CH.sub.2).sub.p OR.sup.4, O(CH.sub.2).sub.q R.sup.5, O(CH.sub.2).sub.r O(CH.sub.2).sub.s OR.sup.6, SO.sub.t A, NR.sup.8 CH.sub.2 Ph, OR.sup.9, succinimidyl etc., A represents alkyl, alkoxycarbonyl, pyridyl, furyl, (CH.sub.2).sub.w C.sub.6 H.sub.4 R.sup.7, 2-benzimidazolyl or 2-benzothiazolyl etc., R.sup.4 represents hydrogen, alkyl, aryl or aralkyl, R.sup.5 represents halo, alkoxycarbonyl, aryl or heteroaryl, R.sup.6 represents hydrogen or alkyl, R.sup.7 represents hydrogen, alkyl, alkoxy or halo, R.sup.8 represents alkyl or acetyl, R.sup.9 represents hydrogen, alkyl or aryl, m is an integer of 2 to 10, n and t is of 0 to 2, p and q is of 1 to 3, r is of 1 to 5 and w is 0 to 1 are disclosed in U.S. Pat. No. 5,045,552. ##STR8## An example of these compounds is Rabeprazole shown in formula (IIf). ##STR9##
A group of compounds having general formula (IIg) where R represents a hydrogen atom, or lower alkyl group; R.sup.1 represents a hydrogen atom, halogen atom, lower alkcoxy group, lower cycloalkoxy group, amido group, substituted phenoxy group, substituted benzyloxy group, lower alkoxy group optionally containing halogen atoms, nitro group, hydroxyl group, lower alkenyloxy group, lower alkylthio group or a group --NR.sup.4 R.sup.5, wherein R.sup.4, R.sup.1 may be same or different and each represent a hydrogen atom, lower alkyl group, or R4, R5 mutually combine together with the nitrogen atom adjacent thereto form a 5-6 membered cyclic structure ; R.sup.2 represents hydrogen, halogen, lower alkyl group, optionally containing halogen atom, lower alkoxy group, optionally containing halogen atom, hydroxyl group, acyl group, lower alkoxycarbonyl group, nitro group, or amino group; R.sup.3 represents a hydrogen, lower alkyl group, lower alkoxymethyl group, lower alkylcarbonyl group, lower alkoxycarbonyl group, carbamoyl group, lower alkylcarbamoyl group, lower alkylcarbonylmethyl group, lower alkoxycarbonylmethyl group, lower acyloxymethyl group, or lower alkylsulfonyl group; n represents 0 or 1 and A represents a methine carbon or nitrogen are disclosed in European Patent application No. 0 434 999. ##STR10## An example of these compounds is Nepaprazole shown in formula (IIh). ##STR11##
A group of compounds having, general formula (IIi) where R.sup.1 represents a straight chain or branched (C.sub.1 -C.sub.8)alkoxy which may be substituted with cycloalkyl or (C.sub.2 -C.sub.4)fluoroalkoxy, R.sup.2 represents hydrogen, methyl or methoxy, R.sup.3 and R.sup.4 represent hydrogen or methyl and may be the same or different are disclosed in European Patent application No. 0 254 588. ##STR12## An example of these compounds is shown in formula (IIj) ##STR13##
A group of compounds having general formula (Ilk) where R.sup.1 to R.sup.4 represents hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkanoyl, (C.sub.1 -C.sub.6)alkoxycarbonyl, halo, fluoroalkyl, fluoroalkoxy, or R2 and R3 together form a group --O(CR.sub.2).sub.m O--, R is hydrogen or fluorine, m is 1 or 2, R.sup.5 and R.sup.6 represents hydrogen, (C.sub.1 -C.sub.6)alkyl, or (C.sub.3 -C.sub.6)cycloalkyl, R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form an azetidino, pyrrolidino, piperazino, N-(C.sub.1 -C.sub.4)alkylpiperazino, piperidino, or morpholino group, and one of R.sup.7 and R.sup.8 is fluorine and the other is hydrogen, fluorine, or (C.sub.1 -C.sub.6)alkyl and n is an integer of 0 to 2 are disclosed in European Patent application No. 0 246 774. ##STR14## An example of this class of compounds is shown in formula (IIl) ##STR15##
A group of compounds having general formula (IIm) where R represents hydrogen or alkanoyl group and n is an integer ranging from 0 to 2, are disclosed in the Japanese Patent application No. 62,108,879. ##STR16## An example of this class of compounds is shown in formula (IIn) ##STR17##
A group of compounds having general formula (IIo) where A denotes --CH.dbd.CH-- or S and, R.sup.1, R.sup.3 and R.sup.4 represents independently of one another, denote hydrogen, or lower alkyl group, R.sup.2 represents hydrogen or lower alkoxy group and n is an integer ranging from 0 to 1 are disclosed in U.S. Pat. No. 4,818,760. ##STR18## An example of this class of compounds is shown in formula (IIp). ##STR19##
A group of compounds having general formula (IIq) where X represents S, SO or SO.sub.2 ; Y represents halogen; R.sup.1 and R.sup.2 are independently hydrogen, or alkyl group; R.sup.3 represents hydrogen, (C.sub.1 -C.sub.8)alkyl, SR.sup.6, N(R.sup.7).sub.2, 1-piperidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, 1-pyrrolidinyl, or a group of formula OR.sup.6 or --O(CH.sub.2).sub.m -Z, wherein R.sup.6 represent (C.sub.1 -C.sub.4)alkyl, (C.sub.2 -C.sub.4)alkenyl, optionally substituted (C.sub.3 -C.sub.10)cycloalkyl, (C.sub.2 -C.sub.5)fluoroalkyl or phenyl or benzyl, each of which is independently substituted with one or more halogen or (C.sub.1 -C.sub.4)alkyl or alkoxy optionally substituted with halogen, R.sup.7 is hydrogen or (C.sub.1 -C.sub.5)alkyl, Z represents a group of formula O(CH.sub.2).sub.p OR.sup.8, O(CH.sub.2).sub.q R.sup.9 or O(CH.sub.2).sub.r O(CH.sub.2).sub.s OR.sup.10 wherein p and q are independently an integer 1 to 3, r and s are independently an integer 1 to 5, R.sup.8 represents hydrogen, lower alkyl, aryl or aralkyl, R.sup.9 is hydrogen, alkoxycarbonyl, aryl or heteroaryl and R.sup.10 is hydrogen or lower alkyl, m is an integer of 2 to 10; and R.sup.4 and R.sup.5 independently from each other represent hydrogen or (C.sub.1 -C.sub.5)alkyl or R.sup.4 and R.sup.3 together with the carbon atoms adjacent to the pyridine ring form a ring, R.sup.3 and R.sup.5 or R.sup.4 and R.sup.3 together represent --CH.dbd.CH--CH.dbd.CH--, O(CH.sub.2).sub.n, O(CH.sub.2).sub.n O, CH.sub.2 (CH.sub.2)n or OCH.dbd.CH--, wherein n represents an integer of 1 to 4 are disclosed in Patent application No. GB 2 295 614. ##STR20## An example of this class of compounds is shown in formula (IIr) ##STR21##